Avimers (short for ''
avidity multimers'') are artificial
proteins that are able to specifically bind to certain
antigens via multiple binding sites. Since they are not structurally related to
antibodies
An antibody (Ab), also known as an immunoglobulin (Ig), is a large, Y-shaped protein used by the immune system to identify and neutralize foreign objects such as pathogenic bacteria and viruses. The antibody recognizes a unique molecule of the ...
, they are classified as a type of
antibody mimetic. Avimers have been developed by the biotechnology company Avidia, now part of
Amgen, as potential new
pharmaceutical drugs.
Structure
Avimers consist of two or more
peptide sequences of 30 to 35
amino acids each, connected by linker peptides. The individual sequences are derived from A
domains of various
membrane receptor
Cell surface receptors (membrane receptors, transmembrane receptors) are receptors that are embedded in the plasma membrane of cells. They act in cell signaling by receiving (binding to) extracellular molecules. They are specialized integra ...
s and have a rigid structure, stabilised by
disulfide bonds and
calcium. Each A domain can bind to a certain
epitope of the target protein. The combination of domains binding to different epitopes of the same protein increases affinity to this protein, an effect known as
avidity (hence the name).
Alternatively, the domains can be directed against epitopes on different target proteins. This approach is similar to the one taken in the development of
bispecific monoclonal antibodies. In a study, the
plasma
Plasma or plasm may refer to:
Science
* Plasma (physics), one of the four fundamental states of matter
* Plasma (mineral), a green translucent silica mineral
* Quark–gluon plasma, a state of matter in quantum chromodynamics
Biology
* Blood pla ...
half-life of an anti-
interleukin 6 avimer could be increased by extending it with an anti-
immunoglobulin G
Immunoglobulin G (Ig G) is a type of antibody. Representing approximately 75% of serum antibodies in humans, IgG is the most common type of antibody found in blood circulation. IgG molecules are created and released by plasma B cells. Each IgG a ...
domain.
Properties
Avimers with two or three domains can bind to their targets in sub-
nanomolar concentrations.
They have improved
heat stability
In materials science and molecular biology, thermostability is the ability of a substance to resist irreversible change in its chemical or physical structure, often by resisting decomposition or polymerization, at a high relative temperatur ...
compared with antibodies, but limited plasma
half-life because of their smaller size. Half-life can be increased by binding them to antibodies.
Production
A library theoretically containing up to 10
23 different A domains serves as a starting point for the development of avimers.
Domains targeting the desired protein are selected with display techniques such as
phage display
Phage display is a laboratory technique for the study of protein–protein, protein–peptide, and protein– DNA interactions that uses bacteriophages (viruses that infect bacteria) to connect proteins with the genetic information that encodes ...
. The most promising species are linked to a second A domain via a short linker peptide, forming a new library. This process can be repeated several times, yielding avimers with an increasing number of domains.
References
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*
{{Engineered antibodies
Antibody mimetics